IMPORTANCE Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia.OBJECTIVE To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia.DESIGN, SETTING, AND PARTICIPANTS This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao(2)/Fio(2)) ratio between 350 and 200 mm Hg were eligible.INTERVENTIONS Patients in the experimental group received intravenous high-titer CP (>= 1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations.MAIN OUTCOMES AND MEASURES The primary outcome was a composite of worsening respiratory failure (Pao(2)/Fio(2) ratio <150 mm Hg) or death within 30 days from randomization.RESULTS Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04).CONCLUSIONS AND RELEVANCE In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days.

Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia: A Randomized Clinical Trial / F. Menichetti, P. Popoli, M. Puopolo, S. Spila Alegiani, G. Tiseo, A. Bartoloni, G.V. De Socio, S. Luchi, P. Blanc, M. Puoti, E. Toschi, M. Massari, L. Palmisano, G. Marano, M. Chiamenti, L. Martinelli, S. Franchi, C. Pallotto, L.R. Suardi, B. Luciani Pasqua, M. Merli, P. Fabiani, L. Bertolucci, B. Borchi, S. Modica, S. Moneta, G. Marchetti, A. d'Arminio Monforte, L. Stoppini, N. Ferracchiato, S. Piconi, C. Fabbri, E. Beccastrini, R. Saccardi, A. Giacometti, S. Esperti, P. Pierotti, L. Bernini, C. Bianco, S. Benedetti, A. Lanzi, P. Bonfanti, M. Massari, S. Sani, A. Saracino, A. Castagna, L. Trabace, M. Lanza, D. Focosi, A. Mazzoni, M. Pistello, M. Falcone. - In: JAMA NETWORK OPEN. - ISSN 2574-3805. - 4:11(2021), pp. e36246.1-e36246.12. [10.1001/jamanetworkopen.2021.36246]

Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia: A Randomized Clinical Trial

Marano, Giuseppe;Chiamenti, Margherita;Martinelli, Laura;Franchi, Silvia;Marchetti, Giulia;d'Arminio Monforte, Antonella;Piconi, Stefania;Bianco, Claudia;Benedetti, Sara;Bonfanti, Paolo;
2021

Abstract

IMPORTANCE Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia.OBJECTIVE To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia.DESIGN, SETTING, AND PARTICIPANTS This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao(2)/Fio(2)) ratio between 350 and 200 mm Hg were eligible.INTERVENTIONS Patients in the experimental group received intravenous high-titer CP (>= 1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations.MAIN OUTCOMES AND MEASURES The primary outcome was a composite of worsening respiratory failure (Pao(2)/Fio(2) ratio <150 mm Hg) or death within 30 days from randomization.RESULTS Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04).CONCLUSIONS AND RELEVANCE In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days.
Aged; COVID-19; Disease Progression; Female; Humans; Italy; Male; Middle Aged; Prospective Studies; SARS-CoV-2; Severity of Illness Index; Standard of Care; Hospital Mortality; Hospitalization; Immunization, Passive; Plasma; Respiratory Insufficiency
Settore MED/17 - Malattie Infettive
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/929331
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